IL105832A - תרכבות פוספונט הטרוציקליות מכילות חנקן, מותמרות ע" י תיו ותכשירי רוקחות המכילים אותן - Google Patents
תרכבות פוספונט הטרוציקליות מכילות חנקן, מותמרות ע" י תיו ותכשירי רוקחות המכילים אותןInfo
- Publication number
- IL105832A IL105832A IL10583293A IL10583293A IL105832A IL 105832 A IL105832 A IL 105832A IL 10583293 A IL10583293 A IL 10583293A IL 10583293 A IL10583293 A IL 10583293A IL 105832 A IL105832 A IL 105832A
- Authority
- IL
- Israel
- Prior art keywords
- compound
- substituted
- alkyl
- unsubstituted
- hydrogen
- Prior art date
Links
- -1 nitrogen-containing heterocyclic phosphonate compounds Chemical class 0.000 title claims description 115
- 239000008194 pharmaceutical composition Chemical class 0.000 title claims description 28
- 150000001875 compounds Chemical class 0.000 claims description 104
- 125000000217 alkyl group Chemical group 0.000 claims description 56
- 125000000623 heterocyclic group Chemical group 0.000 claims description 55
- 229910052739 hydrogen Inorganic materials 0.000 claims description 47
- 239000001257 hydrogen Substances 0.000 claims description 45
- 150000002148 esters Chemical class 0.000 claims description 44
- 229910052757 nitrogen Inorganic materials 0.000 claims description 41
- 239000000203 mixture Substances 0.000 claims description 35
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims description 31
- 239000011575 calcium Substances 0.000 claims description 31
- 229910052791 calcium Inorganic materials 0.000 claims description 31
- 125000001424 substituent group Chemical group 0.000 claims description 30
- 238000011282 treatment Methods 0.000 claims description 27
- 229910019142 PO4 Inorganic materials 0.000 claims description 25
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims description 25
- 239000010452 phosphate Substances 0.000 claims description 25
- 229910052717 sulfur Inorganic materials 0.000 claims description 21
- 125000004429 atom Chemical group 0.000 claims description 19
- 150000002431 hydrogen Chemical group 0.000 claims description 18
- 206010003246 arthritis Diseases 0.000 claims description 17
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 16
- 230000002159 abnormal effect Effects 0.000 claims description 16
- 230000004060 metabolic process Effects 0.000 claims description 15
- 125000003367 polycyclic group Chemical group 0.000 claims description 15
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 15
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 14
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 13
- 125000005842 heteroatom Chemical group 0.000 claims description 12
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 12
- 241000124008 Mammalia Species 0.000 claims description 11
- 239000003795 chemical substances by application Substances 0.000 claims description 11
- 239000002904 solvent Substances 0.000 claims description 10
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 9
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 9
- 239000003814 drug Substances 0.000 claims description 9
- 229910052736 halogen Inorganic materials 0.000 claims description 9
- 150000002367 halogens Chemical class 0.000 claims description 9
- 125000002950 monocyclic group Chemical group 0.000 claims description 9
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 9
- 125000003107 substituted aryl group Chemical group 0.000 claims description 7
- 229910018828 PO3H2 Inorganic materials 0.000 claims description 6
- 239000011230 binding agent Substances 0.000 claims description 6
- 239000000945 filler Substances 0.000 claims description 6
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- 235000013355 food flavoring agent Nutrition 0.000 claims description 6
- 235000003599 food sweetener Nutrition 0.000 claims description 6
- 239000000314 lubricant Substances 0.000 claims description 6
- 239000003755 preservative agent Substances 0.000 claims description 6
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 6
- 239000004094 surface-active agent Substances 0.000 claims description 6
- 239000003765 sweetening agent Substances 0.000 claims description 6
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 4
- 239000007884 disintegrant Substances 0.000 claims description 4
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 2
- 239000007853 buffer solution Substances 0.000 claims description 2
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 2
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims 3
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims 2
- YNGDWRXWKFWCJY-UHFFFAOYSA-N 1,4-Dihydropyridine Chemical compound C1C=CNC=C1 YNGDWRXWKFWCJY-UHFFFAOYSA-N 0.000 claims 1
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 claims 1
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims 1
- IIRVGTWONXBBAW-UHFFFAOYSA-M disodium;dioxido(oxo)phosphanium Chemical compound [Na+].[Na+].[O-][P+]([O-])=O IIRVGTWONXBBAW-UHFFFAOYSA-M 0.000 claims 1
- 230000002265 prevention Effects 0.000 claims 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 63
- ABLZXFCXXLZCGV-UHFFFAOYSA-N Phosphorous acid Chemical class OP(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 description 62
- 229940116254 phosphonic acid Drugs 0.000 description 49
- 239000002253 acid Substances 0.000 description 48
- 230000015572 biosynthetic process Effects 0.000 description 42
- 238000003786 synthesis reaction Methods 0.000 description 39
- 239000000243 solution Substances 0.000 description 36
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 33
- 235000002639 sodium chloride Nutrition 0.000 description 30
- 208000001132 Osteoporosis Diseases 0.000 description 29
- 230000002829 reductive effect Effects 0.000 description 28
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 25
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 25
- 210000000988 bone and bone Anatomy 0.000 description 25
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 25
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 24
- 206010039073 rheumatoid arthritis Diseases 0.000 description 22
- 239000011541 reaction mixture Substances 0.000 description 21
- 150000003839 salts Chemical class 0.000 description 21
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 20
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- 241000700159 Rattus Species 0.000 description 19
- 238000006243 chemical reaction Methods 0.000 description 19
- 238000000034 method Methods 0.000 description 19
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- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 15
- 125000004433 nitrogen atom Chemical group N* 0.000 description 15
- 239000000047 product Substances 0.000 description 15
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 14
- 125000000219 ethylidene group Chemical group [H]C(=[*])C([H])([H])[H] 0.000 description 13
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 12
- 125000006295 amino methylene group Chemical group [H]N(*)C([H])([H])* 0.000 description 12
- 150000001721 carbon Chemical group 0.000 description 12
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 12
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 12
- 239000011593 sulfur Substances 0.000 description 12
- 239000003826 tablet Substances 0.000 description 12
- 150000003573 thiols Chemical class 0.000 description 12
- 239000002775 capsule Substances 0.000 description 11
- 125000004432 carbon atom Chemical group C* 0.000 description 11
- 238000003818 flash chromatography Methods 0.000 description 11
- 239000012990 dithiocarbamate Substances 0.000 description 10
- 125000001183 hydrocarbyl group Chemical group 0.000 description 10
- 239000007924 injection Substances 0.000 description 10
- 238000002347 injection Methods 0.000 description 10
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 10
- 229920006395 saturated elastomer Chemical group 0.000 description 10
- 238000002560 therapeutic procedure Methods 0.000 description 10
- 229940122361 Bisphosphonate Drugs 0.000 description 9
- 208000006386 Bone Resorption Diseases 0.000 description 9
- 239000012988 Dithioester Substances 0.000 description 9
- 208000009386 Experimental Arthritis Diseases 0.000 description 9
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 9
- 125000003118 aryl group Chemical group 0.000 description 9
- 230000024279 bone resorption Effects 0.000 description 9
- 235000019441 ethanol Nutrition 0.000 description 9
- 229910052760 oxygen Inorganic materials 0.000 description 9
- 239000001301 oxygen Substances 0.000 description 9
- 239000000741 silica gel Substances 0.000 description 9
- 229910002027 silica gel Inorganic materials 0.000 description 9
- 229960001866 silicon dioxide Drugs 0.000 description 9
- 208000024891 symptom Diseases 0.000 description 9
- 238000012360 testing method Methods 0.000 description 9
- 239000012298 atmosphere Substances 0.000 description 8
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 8
- 150000004663 bisphosphonates Chemical class 0.000 description 8
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 8
- 201000010099 disease Diseases 0.000 description 8
- 239000010410 layer Substances 0.000 description 8
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 8
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 8
- 230000001575 pathological effect Effects 0.000 description 8
- 238000010992 reflux Methods 0.000 description 8
- 125000000446 sulfanediyl group Chemical group *S* 0.000 description 8
- 206010065687 Bone loss Diseases 0.000 description 7
- 150000007513 acids Chemical class 0.000 description 7
- 230000008021 deposition Effects 0.000 description 7
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 7
- 239000012044 organic layer Substances 0.000 description 7
- 125000004430 oxygen atom Chemical group O* 0.000 description 7
- 238000000746 purification Methods 0.000 description 7
- 238000003756 stirring Methods 0.000 description 7
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 6
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical class [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 150000001356 alkyl thiols Chemical class 0.000 description 6
- 229940079593 drug Drugs 0.000 description 6
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- 150000007970 thio esters Chemical class 0.000 description 6
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 5
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 5
- 229920002472 Starch Polymers 0.000 description 5
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 5
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- UEZVMMHDMIWARA-UHFFFAOYSA-M phosphonate Chemical compound [O-]P(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-M 0.000 description 5
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- 229910052708 sodium Inorganic materials 0.000 description 5
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- IVHVNMLJNASKHW-UHFFFAOYSA-M Chlorphonium chloride Chemical compound [Cl-].CCCC[P+](CCCC)(CCCC)CC1=CC=C(Cl)C=C1Cl IVHVNMLJNASKHW-UHFFFAOYSA-M 0.000 description 4
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- UQEAIHBTYFGYIE-UHFFFAOYSA-N hexamethyldisiloxane Chemical compound C[Si](C)(C)O[Si](C)(C)C UQEAIHBTYFGYIE-UHFFFAOYSA-N 0.000 description 4
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- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 229920003109 sodium starch glycolate Polymers 0.000 description 1
- 239000008109 sodium starch glycolate Substances 0.000 description 1
- 229940079832 sodium starch glycolate Drugs 0.000 description 1
- 229910052979 sodium sulfide Inorganic materials 0.000 description 1
- GRVFOGOEDUUMBP-UHFFFAOYSA-N sodium sulfide (anhydrous) Chemical compound [Na+].[Na+].[S-2] GRVFOGOEDUUMBP-UHFFFAOYSA-N 0.000 description 1
- 210000004872 soft tissue Anatomy 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
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- 238000010972 statistical evaluation Methods 0.000 description 1
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- 210000005065 subchondral bone plate Anatomy 0.000 description 1
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- 235000000346 sugar Nutrition 0.000 description 1
- 125000001273 sulfonato group Chemical group [O-]S(*)(=O)=O 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 230000002522 swelling effect Effects 0.000 description 1
- 238000002636 symptomatic treatment Methods 0.000 description 1
- 201000004595 synovitis Diseases 0.000 description 1
- 238000012385 systemic delivery Methods 0.000 description 1
- 229910052713 technetium Inorganic materials 0.000 description 1
- 229960004989 tetracycline hydrochloride Drugs 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 description 1
- 229940033663 thimerosal Drugs 0.000 description 1
- 210000000115 thoracic cavity Anatomy 0.000 description 1
- 230000036962 time dependent Effects 0.000 description 1
- 125000003944 tolyl group Chemical group 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 238000012384 transportation and delivery Methods 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 235000019731 tricalcium phosphate Nutrition 0.000 description 1
- BDZBKCUKTQZUTL-UHFFFAOYSA-N triethyl phosphite Chemical compound CCOP(OCC)OCC BDZBKCUKTQZUTL-UHFFFAOYSA-N 0.000 description 1
- 229930195735 unsaturated hydrocarbon Natural products 0.000 description 1
- 210000001364 upper extremity Anatomy 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6561—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/12—Drugs for disorders of the metabolism for electrolyte homeostasis
- A61P3/14—Drugs for disorders of the metabolism for electrolyte homeostasis for calcium homeostasis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/38—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)]
- C07F9/3804—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)] not used, see subgroups
- C07F9/3808—Acyclic saturated acids which can have further substituents on alkyl
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/553—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having one nitrogen atom as the only ring hetero atom
- C07F9/5532—Seven-(or more) membered rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/553—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having one nitrogen atom as the only ring hetero atom
- C07F9/572—Five-membered rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/553—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having one nitrogen atom as the only ring hetero atom
- C07F9/576—Six-membered rings
- C07F9/5765—Six-membered rings condensed with carbocyclic rings or carbocyclic ring systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/553—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having one nitrogen atom as the only ring hetero atom
- C07F9/576—Six-membered rings
- C07F9/58—Pyridine rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/553—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having one nitrogen atom as the only ring hetero atom
- C07F9/576—Six-membered rings
- C07F9/59—Hydrogenated pyridine rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/645—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having two nitrogen atoms as the only ring hetero atoms
- C07F9/6503—Five-membered rings
- C07F9/6506—Five-membered rings having the nitrogen atoms in positions 1 and 3
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/645—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having two nitrogen atoms as the only ring hetero atoms
- C07F9/6509—Six-membered rings
- C07F9/6512—Six-membered rings having the nitrogen atoms in positions 1 and 3
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- General Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Rheumatology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Physical Education & Sports Medicine (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Pain & Pain Management (AREA)
- Endocrinology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US89149092A | 1992-05-29 | 1992-05-29 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| IL105832A0 IL105832A0 (en) | 1993-09-22 |
| IL105832A true IL105832A (he) | 1998-08-16 |
Family
ID=25398279
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IL10583293A IL105832A (he) | 1992-05-29 | 1993-05-28 | תרכבות פוספונט הטרוציקליות מכילות חנקן, מותמרות ע" י תיו ותכשירי רוקחות המכילים אותן |
Country Status (20)
| Country | Link |
|---|---|
| US (1) | US5856314A (he) |
| EP (1) | EP0642521A1 (he) |
| JP (1) | JPH07507317A (he) |
| KR (1) | KR100266484B1 (he) |
| CN (1) | CN1039327C (he) |
| AU (1) | AU666741B2 (he) |
| CA (1) | CA2136820C (he) |
| CZ (1) | CZ295994A3 (he) |
| FI (1) | FI945595A0 (he) |
| HU (1) | HUT69731A (he) |
| IL (1) | IL105832A (he) |
| MX (1) | MX9303249A (he) |
| NO (1) | NO305398B1 (he) |
| NZ (1) | NZ253526A (he) |
| PL (1) | PL175046B1 (he) |
| RU (1) | RU2124019C1 (he) |
| SG (1) | SG47603A1 (he) |
| SK (1) | SK144694A3 (he) |
| WO (1) | WO1993024500A1 (he) |
| ZA (1) | ZA933766B (he) |
Families Citing this family (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ATE301129T1 (de) | 1999-05-04 | 2005-08-15 | Strakan Int Ltd | Androgen glykoside und die androgenische aktivität davon |
| AU2583901A (en) | 1999-12-17 | 2001-06-25 | Ariad Pharmaceuticals, Inc. | Proton pump inhibitors |
| AU2756701A (en) * | 2000-01-04 | 2001-07-16 | Regents Of The University Of California, The | Use of low dosage bisphosphonates to inhibit cardiac and arterial calcification |
| US7208481B2 (en) * | 2002-02-19 | 2007-04-24 | Ilex Products, Inc. | Aminodiphosphonate apolipoprotein E modulators |
| WO2005090370A1 (en) | 2004-02-05 | 2005-09-29 | The Regents Of The University Of California | Pharmacologically active agents containing esterified phosphonates and methods for use thereof |
| US20070003608A1 (en) * | 2005-04-08 | 2007-01-04 | Almond Merrick R | Compounds, compositions and methods for the treatment of viral infections and other medical disorders |
| US8642577B2 (en) | 2005-04-08 | 2014-02-04 | Chimerix, Inc. | Compounds, compositions and methods for the treatment of poxvirus infections |
| ES2494295T3 (es) | 2007-06-06 | 2014-09-15 | Basf Se | Uso de un polímero de N-vinilimidazol para mejorar las propiedades determinadoras de valor de soluciones biológicamente fermentadas |
| US8993542B2 (en) * | 2008-01-25 | 2015-03-31 | Chimerix Inc. | Methods of treating viral infections |
| US8614200B2 (en) | 2009-07-21 | 2013-12-24 | Chimerix, Inc. | Compounds, compositions and methods for treating ocular conditions |
| US20120164104A1 (en) | 2009-08-03 | 2012-06-28 | Chimerix, Inc. | Composition and Methods of Treating Viral Infections and Viral Induced Tumors |
| US9006218B2 (en) | 2010-02-12 | 2015-04-14 | Chimerix Inc. | Nucleoside phosphonate salts |
| AU2011248620B2 (en) | 2010-04-26 | 2015-11-26 | Chimerix, Inc. | Methods of treating retroviral infections and related dosage regimes |
| RU2506085C1 (ru) * | 2013-01-30 | 2014-02-10 | Федеральное бюджетное учреждение науки "Государственный научный центр вирусологии и биотехнологии "Вектор" (ФБУН ГНЦ ВБ "Вектор") | Тетраэтил-2-(2,2,6,6-тетраметилпиперидин-4-иламино)-этилен-1,1-бисфосфонат, обладающий противоопухолевой активностью |
| DE202015000809U1 (de) | 2015-02-02 | 2015-02-16 | Basf Se | Copolymere enthaltend Alkylaminoalkylalkoxy(meth)acrylate und deren Verwendung zur Wasserbehandlung |
| JP2019518792A (ja) * | 2016-06-03 | 2019-07-04 | バイオビンク エルエルシー | ビスホスホネート・キノロン複合体及びそれらの用途 |
| US10865220B2 (en) | 2016-06-03 | 2020-12-15 | Biovinc, Llc | Bisphosphonate quinolone conjugates and uses thereof |
Family Cites Families (28)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4208401A (en) * | 1977-08-19 | 1980-06-17 | Colgate-Palmolive Company | Quaternary ammonium alkylene diphosphonate anti-calculus agents |
| DE2745083C2 (de) * | 1977-10-07 | 1985-05-02 | Henkel KGaA, 4000 Düsseldorf | Hydroxydiphosphonsäuren und Verfahren zu deren Herstellung |
| DE2835492A1 (de) * | 1978-08-12 | 1980-02-21 | Bayer Ag | 2-cycloalkyl-pyrimidin(5)yl-(thiono) (thiol)-phosphor-(phosphon)-saeureester bzw. -esteramide, verfahren zu ihrer herstellung sowie ihre verwendung als insektizide, akarizide und nematizide |
| DE3016289A1 (de) * | 1980-04-28 | 1981-10-29 | Henkel KGaA, 4000 Düsseldorf | Verfahren zur herstellung von omega -amino-1-hydroxyalkyliden-1,1-bis-phosphonsaeuren |
| FR2531088B1 (fr) * | 1982-07-29 | 1987-08-28 | Sanofi Sa | Produits anti-inflammatoires derives de l'acide methylenediphosphonique et leur procede de preparation |
| US4588711A (en) * | 1982-11-22 | 1986-05-13 | The Dow Chemical Company | Insecticidal phosphorus derivatives of 6-cycloalkyl-4-pyrimidinols |
| FR2558837B1 (fr) * | 1984-01-26 | 1986-06-27 | Sanofi Sa | Derives de l'acide methylenediphosphonique, procede d'obtention et medicaments antirhumatismaux les contenant |
| DE3428524A1 (de) * | 1984-08-02 | 1986-02-13 | Boehringer Mannheim Gmbh, 6800 Mannheim | Neue diphosphonsaeurederivate, verfahren zu deren herstellung und diese verbindungen enthaltende arzneimittel |
| IL77243A (en) * | 1984-12-21 | 1996-11-14 | Procter & Gamble | Pharmaceutical compositions containing geminal diphosphonic acid compounds and certain such novel compounds |
| US4687768A (en) * | 1984-12-21 | 1987-08-18 | The Procter & Gamble Company | Certain hexahydroindan-2,2-diphosphonic acids useful in treating diseases associated with abnormal calcium and phosphate metabolism |
| US5104863A (en) * | 1984-12-21 | 1992-04-14 | The Procter & Gamble Company | Certain bicycloalkane and azabicycloalkane-1,1-diphosphonic acid derivatives useful for treating diseases associated with abnormal calcium and phosphate metabolism |
| US4902679A (en) * | 1985-12-13 | 1990-02-20 | Norwich Eaton Pharmaceuticals, Inc. | Methods of treating diseases with certain geminal diphosphonates |
| DE3770982D1 (de) * | 1986-04-24 | 1991-08-01 | Fujisawa Pharmaceutical Co | Diphosphonsaeure-verbindungen, verfahren zu deren herstellung und sie enthaltende arzneimittel. |
| DE3776880D1 (de) * | 1986-11-21 | 1992-04-02 | Ciba Geigy Ag | Neue substituierte alkandiphosphonsaeuren. |
| DE3640938A1 (de) * | 1986-11-29 | 1988-06-01 | Boehringer Mannheim Gmbh | Neue diphosphonsaeurederivate, verfahren zu deren herstellung und diese verbindung enthaltende arzneimittel |
| US5071840A (en) * | 1986-12-19 | 1991-12-10 | Norwich Eaton Pharmaceuticals, Inc. | Certain heterocyclic substituted diphosphonate compounds pharmaceutical compositions, and methods of treating abnormal calcium and phosphate metabolism |
| US4868164A (en) * | 1986-12-19 | 1989-09-19 | Norwich Eaton Pharmaceuticals, Inc. | Octahydro-pyridine diphosphonate compounds, pharmaceutical compositions, and methods for treating abnormal calcium and phosphate metabolism |
| IL86951A (he) * | 1987-07-06 | 1996-07-23 | Procter & Gamble Pharma | מתילן פוספונואלקילפוספינטנים ותכשירי רוקחות המכילים אותם |
| ATE90353T1 (de) * | 1987-12-11 | 1993-06-15 | Ciba Geigy Ag | Araliphatylaminoalkandiphosphonsaeuren. |
| US4933472A (en) * | 1988-04-08 | 1990-06-12 | Yamanouchi Pharmaceutical Co., Ltd. | Substituted aminomethylenebis(phosphonic acid) derivatives |
| TW198039B (he) * | 1988-11-28 | 1993-01-11 | Ciba Geigy Ag | |
| AU628158B2 (en) * | 1989-04-03 | 1992-09-10 | Upjohn Company, The | Geminal bisphosphonic acids and derivatives as anti-arthritic agents |
| DE4011777A1 (de) * | 1989-04-14 | 1990-10-18 | Ciba Geigy Ag | N-trisubstituierte aminoalkandiphosphonsaeuren |
| US4922007A (en) * | 1989-06-09 | 1990-05-01 | Merck & Co., Inc. | Process for preparing 4-amino-1-hydroxybutylidene-1,1-bisphosphonic acid or salts thereof |
| AU7165791A (en) * | 1990-01-12 | 1991-08-05 | Rhone-Poulenc Rorer International (Holdings) Inc. | 1-azetidyl and 1-hexamethylenimine alkyl or aryl bisphosphonic acids and their use as pharmacological agents |
| ATE168379T1 (de) * | 1992-05-29 | 1998-08-15 | Procter & Gamble Pharma | Quaternare stickstoff-enthaltende phosphonat- verbindungen zur behandlung abnormalen calzium und phosphat-metabolismus sowie zahnsteinbildung |
| PL175475B1 (pl) * | 1992-05-29 | 1999-01-29 | Procter & Gamble Pharma | Nowe zawierające siarkę związki fosfonianowe |
| US5763611A (en) * | 1992-05-29 | 1998-06-09 | The Procter & Gamble Company | Thio-substituted cyclic phosphonate compounds, pharmaceutical compositions, and methods for treating abnormal calcium and phosphate metabolism |
-
1993
- 1993-05-26 PL PL93306141A patent/PL175046B1/pl unknown
- 1993-05-26 NZ NZ253526A patent/NZ253526A/en unknown
- 1993-05-26 CZ CZ942959A patent/CZ295994A3/cs unknown
- 1993-05-26 EP EP93914153A patent/EP0642521A1/en not_active Ceased
- 1993-05-26 SG SG1996003070A patent/SG47603A1/en unknown
- 1993-05-26 JP JP6500724A patent/JPH07507317A/ja active Pending
- 1993-05-26 SK SK1446-94A patent/SK144694A3/sk unknown
- 1993-05-26 WO PCT/US1993/004979 patent/WO1993024500A1/en not_active Application Discontinuation
- 1993-05-26 AU AU43919/93A patent/AU666741B2/en not_active Ceased
- 1993-05-26 KR KR1019940704305A patent/KR100266484B1/ko not_active IP Right Cessation
- 1993-05-26 CA CA002136820A patent/CA2136820C/en not_active Expired - Fee Related
- 1993-05-26 RU RU94046146A patent/RU2124019C1/ru active
- 1993-05-26 HU HU9403407A patent/HUT69731A/hu unknown
- 1993-05-28 ZA ZA933766A patent/ZA933766B/xx unknown
- 1993-05-28 IL IL10583293A patent/IL105832A/he not_active IP Right Cessation
- 1993-05-29 CN CN93108277A patent/CN1039327C/zh not_active Expired - Fee Related
- 1993-05-31 MX MX9303249A patent/MX9303249A/es not_active Application Discontinuation
-
1994
- 1994-05-09 US US08/240,303 patent/US5856314A/en not_active Expired - Fee Related
- 1994-11-24 NO NO944501A patent/NO305398B1/no not_active IP Right Cessation
- 1994-11-28 FI FI945595A patent/FI945595A0/fi unknown
Also Published As
| Publication number | Publication date |
|---|---|
| JPH07507317A (ja) | 1995-08-10 |
| FI945595A (fi) | 1994-11-28 |
| HU9403407D0 (en) | 1995-02-28 |
| RU94046146A (ru) | 1996-11-27 |
| PL175046B1 (pl) | 1998-10-30 |
| NO944501D0 (no) | 1994-11-24 |
| ZA933766B (en) | 1994-01-20 |
| US5856314A (en) | 1999-01-05 |
| NO944501L (no) | 1995-01-27 |
| CN1085907A (zh) | 1994-04-27 |
| CN1039327C (zh) | 1998-07-29 |
| AU666741B2 (en) | 1996-02-22 |
| CA2136820A1 (en) | 1993-12-09 |
| MX9303249A (es) | 1994-05-31 |
| NZ253526A (en) | 1997-01-29 |
| RU2124019C1 (ru) | 1998-12-27 |
| AU4391993A (en) | 1993-12-30 |
| SG47603A1 (en) | 1998-04-17 |
| IL105832A0 (en) | 1993-09-22 |
| HUT69731A (en) | 1995-09-28 |
| FI945595A0 (fi) | 1994-11-28 |
| WO1993024500A1 (en) | 1993-12-09 |
| CZ295994A3 (en) | 1995-10-18 |
| EP0642521A1 (en) | 1995-03-15 |
| KR950701932A (ko) | 1995-05-17 |
| KR100266484B1 (ko) | 2000-09-15 |
| NO305398B1 (no) | 1999-05-25 |
| SK144694A3 (en) | 1995-06-07 |
| CA2136820C (en) | 1997-09-09 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FF | Patent granted | ||
| KB | Patent renewed | ||
| RH1 | Patent not in force |